Is axillary artery cannulation necessary in type II hybrid aortic arch repair for acute type A aortic dissection?

INTRODUCTION: Axillary artery cannulation (AAC) has been widely employed in total arch replacement surgeries using the frozen elephant trunk (FET) technique for acute type A aortic dissection (ATAAD), showing better clinical results than femoral artery cannulation (FAC). Nevertheless, in type II hybrid arch repair (HAR), FAC is crucial for lower body perfusion. Hence, it is unclear whether AAC remains necessary or if AAC represents a more advantageous method for initiating cardiopulmonary bypass. METHODS: We conducted a study involving patients diagnosed with ATAAD who underwent type II HAR from August 2021 to December 2022. Demographic baseline and intraoperative data were collected, and the postoperative outcomes of patients receiving FAC only were compared with those receiving AAC. RESULTS: There were no significant differences in baseline demographics between patients who underwent FAC alone (n = 46) and those who underwent AAC (n = 39). Patients who underwent AAC showed a lower incidence of transient neurological dysfunction (TND) post-surgery compared to those who underwent FAC (12.8% vs 32.6%, p = .032). There were no significant differences between the groups in terms of postoperative mortality within 30 days, permanent neurological dysfunction (PND), length of stay in the intensive care unit (ICU) and postoperative ward, duration of mechanical ventilation, and other complications. CONCLUSIONS: Axillary artery cannulation may decrease the incidence of postoperative transient neurological dysfunction (TND) in type II HAR for ATAAD. Nonetheless, studies with larger sample sizes are necessary.

Enhancing the catalytic H2 production performance of magnetic Ni-Fe2O3-C catalyst in biomass steam gasification using electromagnetic induction heating.

In this study, a novel magnetic Ni-Fe2O3-C catalyst combined with electromagnetic induction heating in biomass steam gasification was proposed to enhance H2 production. Better catalytic performance for H2 production was observed with the Ni-Fe2O3-C catalyst under induction heating, resulting in an increase in H2 yield from 735.1 to 2271.2 mL/g-biomass (a 209.1 % enhancement). SEM, TGA and XRD analysis demonstrated a significant decrease in coking deposition, caking, and particle agglomeration of the Ni-Fe2O3-C catalyst under induction heating, while maintaining more active sites. Importantly, the benefits of induction heating were also applicable to different magnetic catalysts like Ni-Al2O3-C, Ni-ZrO2-C, and Ni-MgO-C. Experimental results revealed a logarithmic correlation between the increase in H2 yields due to induction heating and the magnetic saturation (Ms) of the catalysts. The Ni-Fe2O3-C catalyst, with a high Ms of 50.9 emu/g, showed the highest catalytic activity for H2 production under induction heating in this study.

Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity.

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti-B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.

CCR2+ monocytes replenish border-associated macrophages in the diseased mouse brain.

Border-associated macrophages (BAMs) are tissue-resident macrophages that reside at the border of the central nervous system (CNS). Since BAMs originate from yolk sac progenitors that do not persist after birth, the means by which this population of cells is maintained is not well understood. Using two-photon microscopy and multiple lineage-tracing strategies, we determine that CCR2+ monocytes are significant contributors to BAM populations following disruptions of CNS homeostasis in adult mice. After BAM depletion, while the residual BAMs possess partial self-repopulation capability, the CCR2+ monocytes are a critical source of the repopulated BAMs. In addition, we demonstrate the existence of CCR2+ monocyte-derived long-lived BAMs in a brain compression model and in a sepsis model after the initial disruption of homeostasis. Our study reveals that the short-lived CCR2+ monocytes transform into long-lived BAM-like cells at the CNS border and subsequently contribute to BAM populations.

Bioenergetic and excitotoxic determinants of cofilactin rod formation.

Cofilactin rods (CARs), which are 1:1 aggregates of cofilin-1 and actin, lead to neurite loss in ischemic stroke and other disorders. The biochemical pathways driving CAR formation are well-established, but how these pathways are engaged under ischemic conditions is less clear. Brain ischemia produces both ATP depletion and glutamate excitotoxicity, both of which have been shown to drive CAR formation in other settings. Here, we show that CARs are formed in cultured neurons exposed to ischemia-like conditions: oxygen-glucose deprivation (OGD), glutamate, or oxidative stress. Of these conditions, only OGD produced significant ATP depletion, showing that ATP depletion is not required for CAR formation. Moreover, the OGD-induced CAR formation was blocked by the glutamate receptor antagonists MK-801 and kynurenic acid; the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors GSK2795039 and apocynin; as well as an ROS scavenger. The findings identify a biochemical pathway leading from OGD to CAR formation in which the glutamate release induced by energy failure leads to activation of neuronal glutamate receptors, which in turn activates NADPH oxidase to generate oxidative stress and CARs.

Transcriptomic Signature of 3D Hierarchical Porous Chip Enriched Exosomes for Early Detection and Progression Monitoring of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non-invasive diagnosis method based on serum markers, such as α-fetoprotein (AFP), and des-γ-carboxy-prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere-coated three-dimensional (3D) hierarchical porous chip, named a SiO2-chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non-HCC and HCC subjects are enriched using an SiO2-chip and performed RNA sequencing to identify HCC-related long non-coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT-1 and EGFR-AS-1 are two HCC-related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT-PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy-based approach for noninvasive and reliable HCC detection is developed.

A Multienzyme Reaction-Mediated Electrochemical Biosensor for Sensitive Detection of Organophosphorus Pesticides.

Ethephon (ETH), a commonly employed growth regulator, poses potential health risks due to its residue in fruits and vegetables, leading to both acute and subchronic toxicity. However, the detection accuracy of ETH is compromised by the color effects of the samples during the detection process. In this work, a multienzyme reaction-mediated electrochemical biosensor (MRMEC) was developed for the sensitive, rapid, and color-interference-resistant determination of ETH. Nanozymes Fe3O4@Au-Pt and graphene nanocomplexes (GN-Au NPs) were prepared as catalysts and signal amplifiers for MRMEC. Acetylcholinesterase (AChE), acetylcholine (ACh), and choline oxidase (CHOx) form a cascade enzyme reaction to produce H2O2 in an electrolytic cell. Fe3O4@Au-Pt has excellent peroxidase-like activity and can catalyze the oxidation of 3,3',5,5'-tetramethvlbenzidine (TMB) in the presence of H2O2, resulting in a decrease in the characteristic peak current of TMB. Based on the inhibitory effect of ETH on AChE, the differential pulse voltammetry (DPV) current signal of TMB was used to detect ETH, offering the limit of detection (LOD) of 2.01 nmol L-1. The MRMEC method effectively analyzed ETH levels in mangoes, showing satisfactory precision (coefficient of variations, 2.88-15.97%) and recovery rate (92.18-110.72%). This biosensor holds promise for detecting various organophosphorus pesticides in food samples.

Hesperetin promotes diabetic wound healing by inhibiting ferroptosis through the activation of SIRT3.

Hesperetin (HST) is a flavonoid compound naturally occurring in citrus fruits and is widespread in various traditional medicinal herbs such as grapefruit peel, orange peel, and tangerine peel. These plant materials are commonly used in traditional Chinese medicine to prepare herbal remedies. The study aimed to investigate the potential molecular mechanisms through which HST reduces ferroptosis in human umbilical vein endothelial cells (HUVECs) and promotes angiogenesis and wound healing. We employed network pharmacology to predict the downstream targets affected by HST. The expression of markers related to ferroptosis was assessed through Western blot (WB) and polymerase chain reaction. Intracellular levels of ferroptosis-related metabolism were examined using glutathione/oxidized glutathione (GSH/GSSG) and malondialdehyde (MDA) assay kits. Mitochondrial status and iron levels within the cells were investigated through staining with Mitosox, FerroOrange, and JC1 staining. Potential downstream direct targets of HST were identified using molecular docking. Additionally, wound healing and neovascularization within the wound site were analyzed using various methods including HE staining, Masson's staining, immunohistochemistry, and Doppler hemodynamics assessment. HST effectively inhibits the elevated levels of intracellular ferroptosis stimulated by ERASTIN. Furthermore, we observed that HST achieves this inhibition of ferroptosis by activating SIRT3. In a diabetic rat wound model, HST significantly promotes wound healing, reducing levels of tissue ferroptosis, consistent with our in vitro findings. This study demonstrates that HST can inhibit the progression of ferroptosis and protect the physiological function of HUVECs by activating SIRT3. HST holds promise as a natural compound for promoting diabetic wound healing.

Mitral valve leaflet blood cyst treated with minimally invasive approach: a case report and review of literature.

INTRODUCTION: Cardiac blood cyst is a very rare benign tumor of the heart in adults. Though it is very common in the first half year of life, it regresses with time and its occurrence is very rare in children older than six months and in adults. Until now less than 100 valvular blood cyst cases have been reported in adults. CASE PRESENTATION: We present a case of a 66-year-old male who presented to us with exertional chest tightness, shortness of breath, and right leg weakness for two weeks. He was diagnosed with a cardiac mass two months ago in another hospital. The physical examination was unremarkable. Abdominal ultrasound showed a cyst in the liver and left kidney. Echocardiography showed a mass-occupying lesion of a cystic nature in the mitral valve with moderate mitral regurgitation. Based on echocardiography findings and computed tomography report, the preliminary diagnosis of mitral valve cystic tumor was made. The patient underwent minimally invasive resection of the cyst. The posterior mitral cusp was repaired and a mitral annuloplasty ring was placed. The postoperative recovery was uneventful. The histopathology report confirmed the diagnosis of a cardiac blood cyst. The patient was followed up for six months without any complications. This case is presented to enrich the medical literature on the cardiac blood cyst. CONCLUSION: Although a cardiac blood cyst is a rare entity in adults, it still should be considered in the differential diagnosis of cardiac tumors. Because the natural history and hemodynamic effects are very diverse, large symptomatic cardiac blood cysts, especially in the left heart should be resected to avoid complications.

Crescent calculator: A webtool enabling objective decision-making for assessment of IgA nephropathy immune activity throughout the disease course.

IgA nephropathy (IgAN) is an immune-mediated glomerulonephritis, posing a challenge for the long-term management. It is crucial to monitor the disease's activity over the disease course. Crescent lesions have been known as an active lesion associated with immune activity. We aimed to develop the Crescent Calculator to aid clinicians in making timely and well-informed decisions throughout the long-term disease course, such as renal biopsies and immunosuppressive therapy. 1,761 patients with biopsy-proven IgAN were recruited from four medical centers in Zhejiang Province, China. 16.9% presented crescent lesions. UPCR, URBC, eGFR and C4 were independently associated with the crescent lesions. By incorporating these variables, the Crescent Calculator was constructed to estimate the likelihood of crescent lesions. The predictor achieved AUC values of over 0.82 in two independent testing datasets. In addition, to fulfill varied clinical needs, multiple classification modes were established. The Crescent Calculator was developed to estimate the risk of crescent lesions for patients with IgAN, assisting clinicians in making timely, objective, and well-informed decisions regarding the need for renal biopsies and more appropriate use of immunosuppressive therapy in patients with IgAN.

Prognostic Value of Immunohistochemistry-based Subtyping Before and After Neoadjuvant Chemotherapy in Patients with Triple-negative Breast Cancer.

To assess the predictive and prognostic value of a subtyping method based on immunohistochemistry in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC). This study included patients with TNBC treated with anthracycline- and taxane-based NAC and curative surgery. Immunohistochemical (IHC) subtyping was performed using core needle biopsy specimens before NAC (pre-NAC) and residual tumors after NAC (post-NAC). Logistic regression was performed to identify predictive biomarkers of pathological complete response (pCR). Invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed using the log-rank test and Cox proportional hazards regression. A total of 230 patients were followed up for a median of 59 months. Clinical lymph node status and the pre-NAC subtype were independent predictors of pCR (P=0.006 and 0.005, respectively). The pre-NAC subtype was an independent prognostic factor for long-term survival (iDFS: P < 0.001, DDFS: P=0.010, and OS: P=0.044). Among patients with residual disease (RD) after NAC, approximately 45% of tumors changed their IHC subtype. Furthermore, the post-NAC subtype, but not the pre-NAC subtype, was strongly associated with the survival of patients with RD (iDFS: P < 0.001, DDFS: P=0.005, and OS: P=0.006). The IHC subtype predicted response to NAC and long-term survival in patients with early TNBC. In patients with RD, almost 45% of the tumors changed subtype after NAC. The IHC subtype should be considered when planning additional therapies pre- and post-NAC.

Rapid intestinal and systemic metabolic reprogramming in an immunosuppressed environment.

Intrinsic metabolism shapes the immune environment associated with immune suppression and tolerance in settings such as organ transplantation and cancer. However, little is known about the metabolic activities in an immunosuppressive environment. In this study, we employed metagenomic, metabolomic, and immunological approaches to profile the early effects of the immunosuppressant drug tacrolimus, antibiotics, or both in gut lumen and circulation using a murine model. Tacrolimus induced rapid and profound alterations in metabolic activities within two days of treatment, prior to alterations in gut microbiota composition and structure. The metabolic profile and gut microbiome after seven days of treatment was distinct from that after two days of treatment, indicating continuous drug effects on both gut microbial ecosystem and host metabolism. The most affected taxonomic groups are Clostriales and Verrucomicrobiae (i.e., Akkermansia muciniphila), and the most affected metabolic pathways included a group of interconnected amino acids, bile acid conjugation, glucose homeostasis, and energy production. Highly correlated metabolic changes were observed between lumen and serum metabolism, supporting their significant interactions. Despite a small sample size, this study explored the largely uncharacterized microbial and metabolic events in an immunosuppressed environment and demonstrated that early changes in metabolic activities can have significant implications that may serve as antecedent biomarkers of immune activation or quiescence. To understand the intricate relationships among gut microbiome, metabolic activities, and immune cells in an immune suppressed environment is a prerequisite for developing strategies to monitor and optimize alloimmune responses that determine transplant outcomes.

Causal association between constipation and risk of colorectal cancer: a bidirectional two-sample Mendelian randomization study.

Background: Colorectal cancer (CRC) is a globally significant health concern, necessitating effective preventive strategies through identifying modifiable risk factors. Constipation, characterized by infrequent bowel movements or difficulty passing stools, has been proposed as a potential CRC risk factor. However, establishing causal links between constipation and CRC remains challenging due to observational study limitations. Methods: Mendelian randomization (MR) utilizes genetic variants as instrumental variables, capitalizing on genetically determined variation to assess causal relationships. In this dual-sample bidirectional MR study, we extracted genetic data from independent cohorts with CRC (Include colon cancer and rectal cancer) and constipation cases. Genome-wide association studies (GWAS) identified constipation and CRC-associated genetic variants used as instruments to infer causality. The bidirectional MR analysis evaluated constipation's impact on CRC risk and the possibility of reverse causation. Results: Employing bidirectional MR, we explored the causal relationship between constipation and CRC using publicly available GWAS data. Analysis of constipation's effect on CRC identified 26 significant SNPs, all with strong instrumental validity. IVW-random effect analysis suggested a potential causal link [OR = 1.002(1.000, 1.004); P = 0.023], although alternative MR approaches were inconclusive. Investigating CRC's impact on constipation, 28 significant SNPs were identified, yet IVW analyses found no causal effect [OR = 0.137(0.007, 2.824); P = 0.198]. Other MR methods also yielded no significant causal association. We analyzed constipation separately from colon and rectal cancer using the same methodology in both directions, and no causal relationship was obtained. Conclusion: Our bidirectional MR study suggests a potential constipation-CRC link, with mixed MR approach outcomes. Limited evidence supports constipation causing CRC. Reliable instruments, minimal heterogeneity, and robust analyses bolster these findings, enriching understanding. Future research should explore additional factors to enhance comprehension and clinical implications.

Off-pump vs. on-pump bypass surgery grafting in diabetic patients with three-vessel disease: a propensity score matching study.

Background: Controversy exists regarding the advantages and risks of off-pump vs. on-pump coronary artery bypass grafting (CABG) for patients with diabetes. We therefore compare the early clinical outcomes of off-pump vs. on-pump procedures for diabetic patients with three-vessel disease. Materials and methods: We conducted a retrospective analysis of clinical data obtained from 548 diabetic patients with three-vessel coronary artery disease who underwent isolated CABG between January 2016 and June 2020. To adjust the differences of baseline characteristics between the off-pump CABG (OPCAB) and on-pump CABG (ONCAB) groups, propensity score matching (PSM) was used. Following 1:1 matching, we selected 187 pairs of patients for further comparison of outcomes within the first 30 days after surgery. Results: The preoperative characteristics of the patients between the two groups were clinically comparable after PSM. The OPCAB group exhibited a significantly higher incidence of incomplete revascularization (27.3% vs. 14.4%; P = 0.002) compared with the ONCAB group. No differences were seen in mortality within 30 days between the matched groups (1.1% vs. 3.7%; P = 0.174). Notably, the OPCAB group had a lower risk of respiratory failure or infection (2.1% vs. 7.0%; P = 0.025), less postoperative stroke (1.1% vs. 4.8%; P = 0.032), and reduced postoperative ventilator assistance time (35.8 ± 33.7 vs. 50.9 ± 64.8; P = 0.005). Conclusion: OPCAB in diabetic patients with three-vessel disease is a safe procedure with reduced early stroke and respiratory complications and similar mortality rate, myocardial infarction, and renal failure requiring dialysis to conventional on-pump revascularization.

Construction of an EMT-related lncRNA prognostic signature for lung adenocarcinoma and functional verification of its hub gene LINC01615.

BACKGROUND: The epithelial-mesenchymal transition (EMT) plays a vital role in the progression of lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) participate in the EMT process as an important regulatory factor and have the potential to serve as prognostic biomarkers. We aimed to construct a novel lncRNA prognostic signature for LUAD based on EMT-related lncRNAs, identify EMT-related hub lncRNA, and investigate its biological functions. METHODS: RNA-seq data, clinical and survival information were obtained from The Cancer Genome Atlas database. The EMT-related lncRNA prognostic signature (EMTscore) was constructed using the Least Absolute Shrinkage and Selection Operator Cox regression analysis. The efficiency of EMTscore in predicting the prognosis of LUAD was evaluated through the area under the time-dependent receiver operating characteristic (ROC) curves. The hub lncRNA of the prognostic signature was selected using a co-expression network map, and its effects on cell proliferation and metastasis were explored by in vitro experiments. RESULTS: We constructed a prognostic signature (EMTscore) containing 8 tumor-high expressed lncRNAs. The EMTscore performed well in predicting overall survival rates with AUC values of 0.708 at 5 years in the training set. EMTscore could independently predict the survival of LUAD, with HR = 4.011 (95% CI 2.430-6.622) in the multivariate Cox regression. Importantly, we identified LINC01615 as the hub lncRNA in the EMTscore and revealed that LINC01615 enhanced the proliferation, migration, and EMT of lung cancer cells. CONCLUSIONS: A new EMT-related lncRNA prognostic signature named EMTscore was developed, and LINC01615 was identified as the hub lncRNA of EMTscore. The hub lncRNA LINC01615 had an oncogenic biological function in LUAD.

Extracorporeal Left Ventricular Assist Device as a Bridge to Surgery for Ventricular Septal Rupture After Acute Myocardial Infarction.

Ventricular septal rupture (VSR) after acute myocardial infarction (AMI) is a rare but often fatal complication. Surgery is considered the preferred treatment, although the optimal timing is discussed. The immediate preoperative hemodynamic status significantly impacts postoperative outcomes, making mechanical circulatory support (MCS) devices crucial for perioperative hemodynamic stability. We present the case of a 61-year-old woman with no remarkable cardiological history admitted to our hospital with a diagnosis of AMI and VSR. Due to hemodynamic instability and cardiogenic shock, we utilized an intra-aortic balloon pump (IABP) and an extracorporeal left ventricular assist device (extra-VAD) as a bridge to surgery. After 17 days of IABP support, the patient experienced hemodynamic instability, elevated lactate levels, pulmonary edema, and eventually bedside endotracheal infiltration inventor-assisted breathing. Subsequently, the IABP was removed, and the patient underwent 6 days of extra-VAD therapy, resulting in hemodynamic stability, a decline in lactate levels, and a reduction in pulmonary edema on X-ray. Surgical coronary artery bypass grafting and VSR repair were successfully performed without periprocedural complications, and the patient was subsequently discharged. Extra-VAD is useful for serious cardiogenic shock in patients with VSR after AMI and may be considered a reasonable approach as a bridge to surgery.

TREM2 mediates MHCII-associated CD4+ T cell response against gliomas.

BACKGROUND: Myeloid cells comprise up to 50% of the total tumor mass in glioblastoma (GBM) and have been implicated in promoting tumor progression and immunosuppression. Modulating the response of myeloid cells to the tumor has emerged as a promising new approach for cancer treatment. In this regard, we focus on the Triggering Receptor Expressed on Myeloid cells 2 (TREM2), which has recently emerged as a novel immune modulator in peripheral tumors. METHODS: We studied the TREM2 expression profile in various patient tumor samples and conducted single-cell transcriptomic analysis in both glioblastoma patients and the GL261 mouse glioma model. We utilized multiple mouse glioma models and employed state-of-the-art techniques such as in vivo two-photon imaging, spectrum flow cytometry, and in vitro co-culture assays to study TREM2 function in myeloid cell-mediated phagocytosis of tumor cells, antigen presentation, and response of CD4+ T cells within the tumor hemispheres. RESULTS: Our research revealed significantly elevated levels of TREM2 expression in brain tumors compared to other types of tumors in patients. TREM2 was predominantly localized in tumor-associated myeloid cells and was highly expressed in nearly all microglia, as well as various subtypes of macrophages. Surprisingly, in pre-clinical glioma models, TREM2 deficiency did not confer a beneficial effect; instead, it accelerated glioma progression. Through detailed investigations, we determined that TREM2 deficiency impaired the ability of tumor-myeloid cells to phagocytose tumor cells and led to reduced expression of MHCII. This deficiency further significantly decreased the presence of CD4+ T cells within the tumor hemispheres. CONCLUSIONS: Our study unveiled a previously unrecognized protective role of tumor-myeloid TREM2. Specifically, we found TREM2 enhance the phagocytosis of tumor cells and promote an immune response by facilitating MHCII-associated CD4+ T cell responses against gliomas.

MS2 Virus-like Particles as a Versatile Peptide Presentation Platform: Insights into the Deterministic Abilities for Accommodating Heterologous Peptide Lengths.

Virus-like particles (VLPs) are nanostructures with the potential to present heterologous peptides at high density, thereby triggering heightened immunogenicity. RNA bacteriophage MS2 VLPs are a compelling delivery platform among them. However, a notable hurdle arises from the immune response toward MS2 coat protein, swiftly eliminating subsequent vaccinations via the same vector. Although larger inserts effectively mask carrier epitopes, current research predominantly focuses on displaying short conserved peptides (<30 aa). A systematic evaluation regarding the deterministic ability of MS2 VLPs as a platform for presenting heterologous peptides remains a gap. In light of this, we employed the "single-chain dimer" paradigm to scrutinize the tolerance of MS2 VLPs for peptide/protein insertions. The results unveiled functional MS2 VLP assembly solely for inserts smaller than 91 aa. Particularly noteworthy is the largest insertion achieved on the MS2 VLPs to date: the RNA helicase A (RHA) dsRNA-binding domains (dsRBD1). Attempts to introduce additional linkers or empty coat subunits fail to augment the expression level or assembly of the MS2 VLPs displaying dsRBD1, affirming 91 aa as the upper threshold for exogenous protein presentation. By illuminating the precise confines of MS2 VLPs in accommodating distinct peptide lengths, our study informs the selection of appropriate peptide and protein dimensions. This revelation not only underscores the scope of MS2 VLPs but also establishes a pivotal reference point, facilitating the strategic manipulation of MS2 VLPs to design next-generation epitope/antibody-based therapeutics.

Role of Charlson comorbidity index in predicting the ICU admission in patients with thoracic aortic aneurysm undergoing surgery.

OBJECTIVES: This study aimed to explore the value of the Charlson comorbidity index (CCI) in predicting ICU admission in patients with aortic aneurysm (AA). METHODS: The clinical data of patients were obtained from the Medical Information Mart for Intensive Care-IV database. The association between CCI and ICU admission was explored by restricted cubic spline (RCS), threshold effect analysis, generalized linear model, logistic regression, interaction, and mediation analyses. Its clinical value was evaluated by decision curve analysis (DCA), receiver operating characteristic curve (ROC), DeLong's test, and net reclassification index (NRI) analyses. RESULTS: The ICU admission was significantly associated with the thoracic AA (TAA), unruptured status, and surgery status. Therefore, 288 candidate patients with unruptured TAA who received surgery were enrolled in the further analysis. We found that CCI was independently associated with the ICU admission of candidates (P = 0.005). Further, their nonlinear relationship was observed (adjusted P = 0.008), and a significant turning point of 6 was identified. The CCI had a favorable performance in predicting ICU admission (area under curve = 0.728) and achieved a better clinical net benefit. New models based on CCI significantly improved the accuracy of prediction. Besides the importance of CCI in ICU admission, CCI also exerted important interaction effect (rather than mediating effects) on the association of other variables (such as age and blood variables) with ICU admission requirements (all P < 0.05). CONCLUSIONS: The CCI is an important predictor of ICU admission after surgery in patients with unruptured TAA.

Fucoxanthin ameliorates endoplasmic reticulum stress and inhibits apoptosis and alleviates intervertebral disc degeneration in rats by upregulating Sirt1.

Endoplasmic reticulum stress (ERS) and apoptosis of nucleus pulposus (NP) cells are considered to be the main pathological factors of intervertebral disc degeneration (IDD). Fucoxanthin (FX), a marine carotenoid extracted from microalgae, has antioxidant, anti-inflammatory, and anticancer properties. The aim of this study was to investigate the effect of FX on NP cells induced by oxidative stress and its molecular mechanism. Primary NP cells of the lumbar vertebrae of rats were extracted and tested in vitro. qRT-PCR, western blot, immunofluorescence, and TUNEL staining were used to detect apoptosis, ERS, extracellular matrix (ECM), and Sirt1-related pathways. In vivo experiments, the recovery of IDD rats was determined by X-ray, hematoxylin and eosin, Safranin-O/Fast Green, Alcian staining, and immunohistochemistry. Our study showed that oxidative stress induced ERS, apoptosis, and ECM degradation in NP cells. After the use of FX, the expression of Sirt1 was up-regulated, the activation of PERK-eIF2α-ATF4-CHOP was decreased, and apoptosis and ECM degradation were decreased. At the same time, FX improved the degree of disc degeneration in rats in vivo. Our study demonstrates the effect of FX on improving IDD in vivo and in vitro, suggesting that FX may be a potential drug for the treatment of IDD.